Objective To study the bioequivalence of two glipizide tablets in healthy Chinese subjects.Methods Randomized,open,single-administration,two-period,self-cross-over trial design was used in the study.There were 28 Chinese healthy subjects in the fasted state and 28 in the fed state,complete repeat cross single dose oral glipizide tablets test preparation or reference preparation 5 mg.The plasma concentration of glipizide was determined by liquid chromatography/tandem mass spectrometry at different time points after administration.The non-compartmental model was used to calculate the pharmacokinetic parameters and evaluate the bioequivalence of the two formulations.Results The main pharmacokinetic parameters of glipizide in the fasted state were as follows:Cmax were(551.60±91.26)and(518.10±105.10)ng·mL-1;AUC0-t were(3 074.33±861.91)and(3 026.77±934.25)h·ng·mL-1;AUC0-∞ were(3 204.85±990.78)and(3 166.35±1 107.36)h ng·mL-1.The parameters of glipizide in the fed state were as follows:Cmax were(517.30±98.97)and(472.80±114.48)ng·mL-1;AUC0-t were(3 001.12±830.87)and(2 932.79±736.35)h·ng·mL-1;AUC0-∞ were(3 067.00±918.84)and(2 997.44±819.14)h·ng·mL-1.The 90％confidence interval of the Cmax,AUC0-t and AUC0-∞ of the test formulation and the reference formulation were from 80.00％to 125.00％.The incidence of adverse events in fasted group and fed group was no serious adverse events.Conclusion The two glipizide tablets were bioequivalent under fasted and fed conditions,and good security.

Objective To investigate changes in the urinary metabolite profiles of children exposed to polycyclic aromatic hydrocarbons(PAHs)during critical brain development and explore their potential link with the intestinal microbiota. Methods Liquid chromatography-tandem mass spectrometry was used to determine ten hydroxyl metabolites of PAHs(OH-PAHs)in 36-month-old children.Subsequently,37 children were categorized into low-and high-exposure groups based on the sum of the ten OH-PAHs.Ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was used to identify non-targeted metabolites in the urine samples.Furthermore,fecal flora abundance was assessed by 16S rRNA gene sequencing using Illumina MiSeq. Results The concentrations of 21 metabolites were significantly higher in the high exposure group than in the low exposure group(variable importance for projection>1,P<0.05).Most of these metabolites were positively correlated with the hydroxyl metabolites of naphthalene,fluorine,and phenanthrene(r=0.336-0.531).The identified differential metabolites primarily belonged to pathways associated with inflammation or proinflammatory states,including amino acid,lipid,and nucleotide metabolism.Additionally,these distinct metabolites were significantly associated with specific intestinal flora abundances(r=0.34-0.55),which were mainly involved in neurodevelopment. Conclusion Higher PAH exposure in young children affected metabolic homeostasis,particularly that of certain gut microbiota-derived metabolites.Further investigation is needed to explore the potential influence of PAHs on the gut microbiota and their possible association with neurodevelopmental outcomes.

OBJECTIVE: To compare the short-term clinical efficacy of SuperCap approach and direct anterior approach in total hip arthroplasty. METHODS: Clinical data of 70 patients who underwent minimally invasive SuperCap approach and DAA THA in January 2016 to June 2017 were retrospective analyzed. These patients were divided into two groups:SuperCap approach group(SuperCap group) and direct anterior approach group(DAA group). There were 15 males and 15 females in SuperCap group, aged from 45 to 71 years old, and the follow-up time ranged from 24 to 30 months. There were 24 males and 16 females in Group B, aged from 51 to 76 years and the follow-up time ranged from 24 to 36 months. Hemoglobin level of the 3rd day after operation, transfusion rate, acetabular abduction angle, anteversion angle and creatine kinase level of the 3rd day after operation, Harris score of 3 months and the last time, VAS score of 1 week and the last time were recorded and compared. Complications were recorded at the final follow-up. RESULTS: All patients were followed up, the follow-up time of SuperCap group ranged from 24 to 30 months, that of DAA group ranged from 24 to 36 months. No significant differences were found in hemoglobin level on the 3rd day after operation, transfusion rate, Harris score or VAS score between two group (P>0.05). There was no significant difference in Harris score between 3 months after operation and the final follow-up in both groups (P>0.05). There were no significant difference in VAS scores of 6 weeks after operation and on the final follow-up neither(P>0.05). The level of creatine kinase in SuperCap group was significant lower than that in DAA group(P<0.05). Until the final follow-up, there was no significant difference in the incidence of complications between the two groups(P>0.05). CONCLUSION The clinical effect of minimally invasive SuperCap approach after total hip arthroplasty is comparable to that of DAA approach with less soft tissue injury. Patients can recover rapidly after operation and it is a safe and effective surgical approach for surgeons with short learning curve.
Male ; Female ; Humans ; Middle Aged ; Aged ; Arthroplasty, Replacement, Hip ; Retrospective Studies ; Antiviral Agents ; Treatment Outcome ; Creatine Kinase ; Hemoglobins

Child ; Humans ; Bronchoscopy/methods* ; Biopsy/methods* ; Lung/pathology*

Objective:To explore the association of DNA methylation with immune response to hepatitis B (HepB) vaccine in Han nationality children from Guangxi province.Methods:A total of 263 children aged 8-9 months who had completed HepB immunization program were recruited from three hospitals in Guangxi province by using unmatched case-control method. Children with the HepB surface antibody concentration(Anti -HBs)<100 mIU/ml was set as the case group and ≥100 mIU/ml as the control group. Multiplex PCR and heavy sulfite sequencing were used to treat the samples. Illumina platform was used for high-throughput DNA methylation sequencing of IFNG gene target regions and CpG sites. Unconditional logistic regression was used to analyze the association between cytosine-phospho-guanosine DNA methylation at 18 loci of IFNG gene and HepB immune response level. Results:There were 104 children in the case group and 159 in the control group. The median ( Q1, Q3) level of anti -HBs in two groups were 62.34 (30.06, 98.88) mIU/ml and 1 089.10 (710.35, 1 233.45) mIU/ml. The methylation levels of IFNG_1 gene 44 and 93 locus in the case group were higher than those in the control group ( P<0.05). The unconditional logistic regression model showed that the DNA methylation level of IFNG_1 gene at 44 ( OR=1.18, 95% CI: 1.03-1.35) and 93 ( OR=1.21, 95% CI: 1.07-1.38) locus was associated with the HepB response level. Conclusion:The changes of DNA methylation at locus 44 and 93 of IFNG_1 gene may be relevant factors affecting the response level of HepB in Han nationality children from Guangxi province.

Objective: To investigate the acute and long-term outcome of catheter ablation for the treatment of ventricular tachycardia (VT) in patients with arrhythmogenic left ventricular cardiomyopathy (ALVC). Methods: This retrospective, cross-sectional study enrolled ALVC patients undergoing radiofrequency ablation for the treatment of VT at the First Affiliated Hospital of Nanjing Medical University from January 2011 to December 2018 and collected their clinical characteristics and intraoperative electrophysiological examination. Patients were followed up every 6 months after radiofrequency ablation until August 2021. Echocardiographic results and VT recurrence post radiofrequency ablation were analysed. Results: Totally 12 patients were enrolled (mean age: (42±15) years, 11 males(11/12)). The mean of left ventricular end diastolic diameter (LVDd) and left ventricular ejection fraction (LVEF) were (51±5)mm and (65±5)%, respectively. Twelve VTs were induced in 10 patients during the electrophysiological study, and the mean tachycardia cycle length was (293±65) ms. Three-dimensional substrate mapping revealed the diseased area at endocardial site in one patient, at epicardial sites in the other 11 patients (involved endocardial sites in 2 cases) with the basal part near the mitral annulus being the predilection for the substrate (10/11). After the catheter ablation at the endocardial and epicardial sites respectively, the complete procedure endpoint was achieved in all patients (VT cannot be induced post ablation). The median follow-up time was 65 (25, 123) months. One patient was lost to follow-up, and the other 11 patients survived without VT. No significant cardiac function deterioration was detected by the echocardiographic examination ((51±5)mm vs. (52±5)mm, P>0.05 for LVDd, (65±5)% vs. (60±6)%, P>0.05 for LVEF) at the end of follow-up. Conclusion: After radiofrequency ablation, the complete procedure endpoint is achieved in ALVC patients, and the catheter ablation provides long-term ventricular tachycardia control during the long-term follow-up.
Adult ; Cardiomyopathies ; Catheter Ablation ; Cross-Sectional Studies ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Pericardium/surgery* ; Recurrence ; Retrospective Studies ; Stroke Volume ; Tachycardia, Ventricular/surgery* ; Treatment Outcome ; Ventricular Function, Left

The detection method of characteristic spectrum for reference samples was established by preparing 15 batches of the reference samples of Huagan Decoction, and the peak attribution and the similarity range in the characteristic spectrum were clarified. The ranges of paste-forming rate, content, and transfer rate of the index components including geniposide, paeonol, and paeoniflorin were analyzed. The key quality attribute of the reference samples of Huagan Decoction was defined. The results showed that the 15 batches of the reference samples of Huagan Decoction had good similarities in the characteristic spectrum, which were all higher than 0.9. According to the information of characteristic peak, there were 18 characteristic peaks in the whole prescription, including seven common characteristic peaks from green tangerine peel and dried tangerine peel, four characteristic peaks from tree peony root bark(three of them were common characteristic peaks from tree peony root bark and red peony root), five characteristic peaks from cape jasmine fruit, one characteristic peak from paniculate bolbostemma, and one characteristic peak from oriental waterplantain rhizome.The paste-forming rate of the 15 batches of reference samples was 14.73%-18.83%. The content of geniposide was 1.68%-2.87%, with the average transfer rate of 70.05%±11.13%. The content of paeonol was 0.10%-0.16%, with the average transfer rate of 9.38%±1.78%. The content of paeoniflorin was 1.94%-2.74%, with the average transfer rate of 36.69%±4.63%. This study analyzed the quality value transfer of the reference samples of Huagan Decoction by the evaluation mode of combining the characteristic spectrum, the paste-forming rate, and the content of index components. The findings of this study initially established a stable and feasible standard decoction evaluation method and provided references for the quality control and the subsequent development of relevant preparations of Huagan Decoction.
Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; Paeonia ; Prescriptions ; Quality Control

The present study designed and prepared near-infrared responsive sinomenine hydrochloride(SIN) reservoir microneedles and evaluated the feasibility of this type of microneedles in increasing the drug loading and transdermal absorption by characterizing their mechanical properties and in vitro release characteristics.SIN was selected as the model drug, and methoxy poly(ethylene glycol) poly(caprolactone)(mPEG-PCL) copolymers and indocyanine green(ICG) were employed as amphiphilic block copolymers and light inductor to prepare near-infrared responsive nanoparticles.Based on the preparation principle of bubble microneedles, near-infrared responsive SIN reservoir microneedles were designed and prepared.The features of the near-infrared responsive SIN reservoir microneedles were characterized by measuring the morphology, length, mechanical properties, and skin penetration of microneedles.Meanwhile, the drug release performance of reservoir microneedles was evaluated by in vitro release assay.The results showed that the prepared SIN microneedles were conical, with an exposed tip height of about 650 μm.Each needle could load about 0.5 mg of drugs per square centi-meter, and this type of microneedle showed good mechanical properties and performance in skin penetration.The results of the in vitro release assay showed that the 24 h cumulative release per unit area and release rate of the microneedle were 825.61 μg·cm~(-2) and 74.3%, respectively, which indicated that its release kinetics was in line with the first-order kinetic model.This study preliminarily proved that the reservoir microneedle could effectively increase the drug loading with good mechanical properties and release perfor-mance.
Drug Delivery Systems/methods* ; Drug Liberation ; Indocyanine Green ; Morphinans ; Needles ; Polyethylene Glycols

Objective: To investigate a SARS-CoV-2 epidemic reported in Rongcheng City, Weihai, Shandong Province. Methods: The SARS-CoV-2 nucleic acid positive patients and their close contacts were investigated, and the whole genome sequencing and genetic evolution analysis of 9 variant viruses were carried out. An infection source investigation and analysis were carried out from two sources of home and abroad, and three aspects of human, material and environment. Results: A total of 15 asymptomatic infections were reported in this epidemic, including 13 cases as employees of workshop of aquatic products processing company, with an infection rate of 21.67% (13/60). Two cases were infected people's neighbors in the same village (conjugal relation). The first six positive persons were processing workers engaged in the first process of removing squid viscera in the workshop of the company. The nucleic acid Ct value of the first time were concentrated between 15 and 29, suggesting that the virus load was high, which was suspected to be caused by one-time homologous exposure. The whole genome sequence of 9 SARS-CoV-2 strains was highly homologous, belonging to VOC/Gamma (Lineage P.1.15). No highly homologous sequences were found from previous native and imported cases in China. It was highly homologous with the six virus sequences sampled from May 5 to 26, 2021 uploaded by Chile. The infection source investigation showed that the company had used the squid raw materials captured in the ocean near Chile and Argentina from May to June 2021 over the last 14 days. Many samples of raw materials, products and their outer packages in the inventory were tested positive for nucleic acid. Conclusion: This epidemic is the first local epidemic caused by the VOC/Gamma of SARS-CoV-2 in China. It is speculated that the VOC/Gamma, which was prevalent in South America from May to June 2021, could be imported into China through frozen squid.
Humans ; SARS-CoV-2 ; COVID-19 ; Epidemics ; China/epidemiology*

Objective: To investigate the regularity of sensory recovery after repairing the wounds on the wrist and back of hand with anterolateral femoral flap without nerve anastomosis. Methods: A cross-sectional study was conducted. From January 2018 to December 2020, patients who underwent free anterolateral femoral flaps without nerve anastomosis to repair wounds on the wrist and back of hand and met the inclusion criteria in Changshu Hai Yu Health Centre and Suzhou Ruihua Orthopedic Hospital were included in this study. Depending on the time interval between the day of the patient's surgery and the day of the cross-sectional survey, 80 patients were divided into 6-month group (15 males and 5 females, aged 22-63 years), 12-month group (16 males and 4 females, aged 21-65 years), 18-month group (15 males and 5 females, aged 25-61 years), and 24-month group (14 males and 6 females, aged 20-65 years), with 20 patients in each group. The area of skin and soft tissue defects after debridement ranged from 6.0 cm×4.5 cm to 18.0 cm×9.0 cm. Anterolateral femoral flaps were cut with areas of 7 cm×5 cm to 20 cm×10 cm and a thickness of 1.0 to 2.5 cm. Each transplanted flap was divided into A (proximal), B/D (bilateral), C (distal), and E (central) regions. The pain sensation, touch sensation, cold sensation, warmth sensation, and two-point discrimination (2-PD) in the aforementioned five regions and the differences in the five senses of the whole flap were tested and compared. Data were statistically analyzed with one-way analysis of variance, Fisher's exact probability test, chi-square test, or McNemar test. Results: In A region of anterolateral femoral flap without nerve anastomosis, compared with those in 6-month group, the pain sensation, touch sensation, cold sensation, and warmth sensation of flap of patients in 12-month group were significantly recovered (with χ² values of 10.10, 14.55, 12.13, and 4.29, respectively, P<0.05 or P<0.01); compared with that in 12-month group, the warmth sensation of flap of patients in 18-month group recovered significantly (χ²=5.23, P<0.05). In B region, compared with those in 6-month group, the pain sensation, touch sensation, and cold sensation of flap of patients in 12-month group recovered significantly (with χ² values of 5.58, 3.96, and 4.29, respectively, P<0.05); compared with those in 12-month group, the pain sensation, touch sensation, cold sensation, and warmth sensation of flap of patients in 18-month group recovered significantly (with χ² values of 5.58, 3.96, 7.03, and 12.38, respectively, P<0.05 or P<0.01). In C region, compared with that in 6-month group, the pain sensation of flap of patients in 12-month group recovered significantly (χ²=4.80, P<0.05); Compared with that in 12-month group, the warmth sensation of flap of patients in 18-month group recovered significantly (χ²=10.16, P<0.01). In D region, compared with those in 6-month group, the pain sensation, touch sensation, and cold sensation of flap of patients in 12-month group recovered significantly (with χ² values of 5.58, 4.29, and 3.96, respectively, P<0.05); compared with those in 12-month group, the pain sensation, touch sensation, cold sensation, and warmth sensation of flap of patients in 18-month group recovered significantly (with χ² values of 5.58, 4.29, 3.96, and 10.10, respectively, P<0.05 or P<0.01). In E region, compared with that in 6-month group, the cold sensation of flap of patients in 12-month group recovered significantly (χ²=4.80, P<0.05); compared with those in 12-month group, the pain sensation, touch sensation, and warmth sensation of flap of patients in 18-month group recovered significantly (with χ² values of 6.47, 4.91, and 9.23, respectively, P<0.05 or P<0.01). The five senses in the 5 regions of flap of patients in 24-month group were similar to those in 18-month group (P>0.05). The recovery of 2-PD in the 5 regions of flap of patients was similar between the two adjacent groups (P>0.05). In 12-month group, the recoveries of pain sensation, touch sensation, and cold sensation of flap of patients in A region were better than those in the other 4 regions (P<0.05 or P<0.01), the recovery of warmth sensation was better than that of B region, C region, and E region (P<0.05 or P<0.01); in 18-month group, the recovery of pain sensation, touch sensation, cold sensation, and warmth sensation of flap of patients in A region of was better than those in area C region (P<0.05). Compared with those in 6-month group, the pain sensation, touch sensation, and cold sensation of the whole flap of patients in 12-month group recovered significantly (with χ² values of 7.62, 7.03, and 5.58, respectively, P<0.05 or P<0.01). Compared with the 12-month group in which 10, 11, 10, and 4 patients had a recovery of pain, touch sensation, cold sensation, and warmth sensation in the whole flap, the 18-month group had significantly more patients with sensations recovered, which were 17, 17, 16, and 14, respectively (with χ² values of 5.58, 4.29, 3.96, and 10.10, respectively, P<0.05 or P<0.01). The five senses of the whole flap of patients in 24-month group were similar to those in 18-month group (P>0.05). Conclusions: In the anterolateral femoral flap without nerve anastomosis for repairing wounds on the wrist and back of hand, the sensation gradually recovered from the proximal end to the distal end. The sensation of touch, pain, and cold began to recover from 6 months after operation, and entered the stable recover period at 18 months after operation. Warmth sensation began to recover from 12 months after operation, and entered the stable recovery period at 18 months after operation. The 2-PD of most flaps was still not recovered 2-year after operation.
Male ; Female ; Humans ; Wrist ; Cross-Sectional Studies ; Touch/physiology* ; Pain ; Anastomosis, Surgical